Heparan sulfate proteoglycan (HSPGs) structure consists of a core protein to which one or more linear glycosaminoglycans (GAGs) chains are attached at specific serine-glycine residues. Heparan sulfates (HSs) have complex sulfated domain structures, which are initially synthesized as non-sulfated polysaccharides of D-glucuronic acid-N-acetyl-D-glucosamine (GlcA-GlcNAc) repeats (1-4). Concurrent with polymerization of the HS chain, a series of enzymatic modifications occur that generate the diverse sulphated domains at intervals along a growing chain. The non-template-driven diversity of HS structure thus is able to give rise to a wide range of biological functions.
Several studies have demonstrated that the binding of growth factors to HS and thus giving rise to mitogenic activity happens only when specific structural features are present within the HS chain (5). Such features include sulfation at specific positions within a disaccharide; 6-O sulphated, N-sulfated glucosamine and 2-O sulfated iduronic acid residues are particularly important, and minimum binding sequences are generally at least 5-6 disaccharides in length (6-8). The precise structures of HS that are involved in these interactions have remained elusive. Knowledge of the variations in composition and organization of HS from different cells and tissues is becoming increasingly essential as attempts are made to elucidate the relationship between HS structure and function. Each tissue type bears a unique complement of HS structures that may also vary at different stages of tissue development (4,9). It is clear that particular heparan sulphate structures are expressed in different tissue types and at different time during development, and these different structures are selectively recognized by heparan sulphate binding proteins; thus for example, differing complements of HS appear to change the way that heparin/HS-dependent growth factors such as the FGFs exert their mitogenic and differentiative effects within developing tissues (10).
Our group has previously shown that HS plays a role in osteogenic differentiation of a preosteoblast MC3T3 cells (11), furthermore, exogenous application of HS to cultures of rat bone marrow stem cells (rMSCs) stimulate their proliferation leading to increased expression of osteogenic markers and enhanced bone nodule formation (12). In recent years human mesenchymal stem cells (hMSC) have been demonstrated to be an alternative cell source for tissue engineering applications. These cells are easy to isolate and can be highly expanded by various tissue culture techniques. These cells are differentiated into a variety of mesenchymal tissues (13), such as osteoblasts (14,15), adipocytes (16), myocytes, astrocytes and neurons (17,18).
Recently gender specific HS were purified from murine tissues and showed that the disaccharide composition of HS chains from the same tissue with different genders are structurally different (19). However comparative structural and functional analysis of the gender specific HS from murine tissue have not been undertaken to date.